Metabolic engineering of Saccharomyces cerevisiae for linalool production

Abstract

Objectives: To engineer the yeast Saccharomyces cerevisiae for the heterologous production of linalool.

Results: Expression of linalool synthase gene from Lavandula angustifolia enabled heterologous production of linalool in S. cerevisiae. Downregulation of ERG9 gene, that encodes squalene synthase, by replacing its native promoter with the repressible MET3 promoter in the presence of methionine resulted in accumulation of 78 µg linalool l(-1) in the culture medium. This was more than twice that produced by the control strain. The highest linalool titer was obtained by combined repression of ERG9 and overexpression of tHMG1. The yeast strain harboring both modifications produced 95 μg linalool l(-1).

Conclusions: Although overexpression of tHMG1 and downregulation of ERG9 enhanced linalool titers threefold in the engineered yeast strain, alleviating linalool toxicity is necessary for further improvement of linalool biosynthesis in yeast.

Keywords: Lavandula angustifolia; Linalool; Linalool synthase; Metabolic engineering; Monoterpene; Saccharomyces cerevisiae.